More Ketamine Use in Refractory Status Epilepticus

Studies needed to determine where it belongs in treatment algorithm

Action Points

Note that this study was published as an abstract and presented at a conference. These data and conclusions should be considered to be preliminary until published in a peer-reviewed journal.

A retrospective analysis of data from the Pediatric Hospital Information System databse showed that use of ketamine for refractory status epilepticus in children, though rare, has increased between the years 2010 and 2014.

The efficacy of ketamine use in refractory status epilepticus remains to be studied.

PHILADELPHIA -- Ketamine has been gaining as rescue therapy for the most refractory cases of status epilepticus in kids, researchers reported here.

"We see this as a call to action," Grinspan said during a press briefing. "We should be studying ketamine for status epilepticus to understand its role and if it has the potential to improve outcomes for these children."

In status epilepticus, patients continuously seize, and the condition has a high mortality rate -- somewhere in the range of 10% to 30%, Grinspan said.

First-line treatment is a benzodiazepine, typically midazolam, followed by a second-line anti-epileptic agent if that doesn't work. Pentobarbital is typically used as a third-line agent, but it has several drawbacks, including the potential to cause cardiac depression.

Ketamine is increasingly being used either in place of or after pentobarbital in children with status epilepticus, particularly because of its good safety profile. It's also being increasingly used in other conditions, including depression.

To get a better idea of just how often ketamine is being used in status epilepticus, Grinspan and Keros conducted a retrospective analysis of data from the Pediatric Hospital Information System (PHIS) database. This networks collects data on demographics, diagnostic codes, and billing information for lab tests, procedures, and medications at 45 children's hospitals in North America.

They created an algorithm to determine which patients used ketamine or pentobarbital or both. They then tested the algorithm on a validation dataset and found it had positive predictive value of 100% and sensitivity of 75% for ketamine detection, and a PPV of 82% and sensitivity of 93% for pentobarbital.

Overall, there were a total of 711 cases of refractory status epilepticus: 630 kids were treated with pentobarbital, 33 with ketamine, and 48 with both drugs.

They found that ketamine use in the condition rose from 2010 to 2014, both in terms of the number of centers using it and the number of patients treated with it. In 2010, it was used at two hospitals, but by 2014 it was used in seven hospitals, and cases grew from two per half year to nine per half year during that time, they reported.

Children treated with ketamine did have longer stays in the PICU, longer EEG monitoring, more frequent use of medicines to treat low blood pressure, and longer ventilator use, they found.

Grinspan and Keros said this finding is consistent with what happens in their own practice, since ketamine is typically reserved for the most challenging cases.

They warned that their research can't explain why ketamine use is increasing, but they speculated that more clinicians are reading about it in case reports, and are experimenting with it after hearing about its potential efficacy and lack of side effects.

They also noted that their study doesn't begin to get at whether the drug is actually effective in this population. Nor does it shed light on where in the treatment algorithm ketamine should be used -- although Grinspan said it isn't likely to be used as a first-line agent any time soon.

"We know very well that the first-line treatment should be a benzodiazepine, and we have pretty good data on second-line treatments, which involve a variety of anti-epileptic drugs. After that, we don't know, " Grinspan said.

"I think the role for ketamine is third-, fourth-, or fifth-line, but that's going to take several years to work out," he said. "While ketamine shows promise for moving up the chain, we want to be cautious that if we change our practice, we do so based on evidence."

Grinspan and Keros disclosed no financial relationships with industry.